It's been several years since COVID-19 vaccines from Pfizer and Moderna jumped
to the top of the pharma industry's sales charts, displacing longtime stalwarts
with unprecedented sales. But, as 2023 featured major patent expirations, the
rise of weight loss drugs and other new dynamics, the year’s ranking of the top 10 drugs by global sales featured its fair share of surprises.
Merck’s
oncology king Keytruda rose to the top last year, adding yet another feather in
its cap. With more than 30 indications across various cancer types and stages,
the PD-L1 inhibitor shows no signs of stopping.
With $25 billion in
global sales, the drug accounted for about 40% of Merck’s total revenue last
year. Keytruda's sales are expected to reach $30 billion this year.
Keytruda
had previously fallen right behind AbbVie's Humira, which held the title of the
world’s bestselling drug for nine years in a row until Pfizer and BioNTech’s
Comirnaty knocked AbbVie’s Humira off its perch in 2021.
Now at No. 2
on the list, Humira has managed to keep a top spot after facing an influx of
biosimilar competition following its U.S. loss of exclusivity. Other meds that
have faced recent copycat competition can’t say the same, such as Bristol Myers
Squibb’s Revlimid.
After comfortably being a top 5 medicine for years, Revlimid started facing
generics in 2022, and, last year, the copycats pushed the blood cancer med all
the way down to the bottom of the list at 19. In just two years, Revlimid’s
yearly sales were nearly halved.
Aside from the usual suspects near
the top of the list, such as BMS and Pfizer’s blood thinner Eliquis and Gilead
Sciences' leading HIV med Biktarvy, a new entry from Novo Nordisk reflects
perhaps the year’s hottest drug arena.
Ozempic and its semaglutide-based counterparts were the names on
everybody’s lips last year, putting a major spotlight on the obesity field
and prompting a wave of drugmakers to scramble to develop their own
offerings.
Novo’s Ozempic has been approved by the FDA to treat Type 2 diabetes since
2017, but it has rapidly gained popularity in recent years for its weight
loss benefits. The fervent demand spread to other meds in the class, and,
now, Novo markets a dedicated obesity brand in Wegovy.
It's likely that 2024’s rankings will include more drugs from the GLP-1
drug class. GLP-1 products are expected to take the baton for the bestselling
drug class from PD-1 inhibitors this year with close to $50 billion in annual
sales, GlobalData has predicted. Other new additions to the top 20 drug rankings include
Novartis’ heart med Entresto and AbbVie’s Skyrizi, which is in line to surpass
Humira sales as early as this year.
1. Keytruda
Keytruda is the world's bestselling cancer drug by a large
margin. (Merck & Co.)
Company: Merck & Co.
2023 sales: $25
billion
Diseases: Melanoma, non-small cell lung cancer, head and
neck cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell
lymphoma, bladder cancer, microsatellite instability-high or mismatch repair
deficient cancer, gastric cancer, esophageal cancer, cervical cancer, liver
cancer, biliary tract cancer, Merkel cell carcinoma, kidney cancer,
endometrial cancer, tumor mutational burden-high cancer, cutaneous squamous
cell carcinoma, triple-negative breast cancer.
After AbbVie's Humira lost U.S. market exclusivity and as demand for COVID
vaccines plummeted at the end of the pandemic, Merck & Co.’s Keytruda was
finally able to claim the title of the world’s bestselling medicine in 2023. But its reign
may be short-lived.
In 2023, Keytruda’s sales grew 21% at constant exchange rates, reaching $25
billion. At the same time, as GLP-1 diabetes and obesity drugs take the
world by storm, Novo Nordisk’s semaglutide franchise—Rybelsus, Ozempic and
Wegovy—together generated 145.8 billion Danish kroner ($21.1 billion). That
marked a nearly 90% surge over 2022.
The three semaglutide brands continued their seemingly unstoppable growth
into 2024. Their first-quarter sales collectively jumped 48% year over year
to 42.2 billion Danish kroner ($6.1 billion), inching even closer to
Keytruda’s $6.9 billion haul, which represented a 20% increase over the same
period last year.
Keytruda is no doubt the world's bestselling cancer drug. The next oncology
asset on our list, Bristol Myers Squibb and Ono Pharma’s rival PD-1 inhibitor
Opdivo, generated $10 billion last year. Johnson & Johnson recorded $9.7
billion for its anti-CD38 multiple myeloma drug Darzalex.
Keytruda scored two high-profile FDA approvals last year, although one of them
wasn’t specifically about the PD-1 drug itself.
In October, the FDA greenlighted Keytruda as part of a continued neoadjuvant-adjuvant therapy used
around surgery in resectable non-small cell lung cancer, making it the first
PD-1/L1 inhibitor regimen that’s used both before and after surgery.
The approval was accompanied by phase 3 data from the KEYNOTE-671 trial
showing that, compared with presurgical chemo alone, the addition of
Keytruda around surgery significantly cut the risk of death by 28%.
Despite perioperative Keytruda’s overall survival win, it remains unclear
whether a checkpoint inhibitor is necessary both before and after surgery
for all approved non-small cell lung cancer cases. The FDA has indicated it
wants to tease out the exact contribution of each phase of treatment to the
entire regimen. The ultimate length of treatment will affect Keytruda’s
long-term sales potential.
In another major feat, a combination of Keytruda and Astellas and
Pfizer’s Padcev won full FDA approval as a first-line treatment for advanced bladder cancer—regardless of
the patient’s eligibility for chemotherapy. The approval came after the
phase 3 EV-302 trial linked the Keytruda-Padcev combo to a 53% reduction
in the risk of death compared with chemo. The results were welcomed with a
standing ovation at the European Society for Medical Oncology meeting last
year.
But the EV-302 readout was viewed as more of a success for Padcev and the
antibody-drug conjugate modality, especially given Keytruda’s
previous stumbles in first-line bladder cancer as a monotherapy and as part of a
combination with traditional chemotherapy. Nevertheless, the EV-302
regimen speaks to Keytruda’s appeal as the combination partner of choice
for newer drugs. Another candidate taking that approach is Moderna and
Merck’s individualized cancer vaccine, mRNA-4157 (V940). The shot’s cocktail with Keytruda has drawn much interest because of
its promising midphase data in resected melanoma.
However, not all attempts to pair Keytruda up have been successful. Some
of the notable failures include Keytruda’s combos with
AstraZeneca-partnered Lynparza and Eisai-shared Lenvima.
As Keytruda is slated to fall off the patent cliff in 2028, Merck has been
working on
a subcutaneous version to potentially soften the blow. However, Merck is
behind its rivals BMS and Roche in terms of developing more convenient
injections of their PD-1/L1 offerings.
2. Humira
Over the years, AbbVie faced criticisms that price hikes and
aggressive patent strategies drove its star drug's performance. (AbbVie)
Company:
AbbVie
2023 sales: $14.4 billion
Disease: Rheumatoid arthritis,
juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis,
Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis
suppurativa and uveitis.
While AbbVie largely played it cool in
the face of a steady stream of Humira biosimilars last year, the onslaught
of copycat biologics ultimately caught up to the autoimmune megablockbuster
in the final stretch of 2023.
Humira, also known as adalimumab, once sat atop the throne as the world’s
bestselling prescription medicine, prompting AbbVie to deploy its infamous
“patent thicket” to protect the drug’s sales for many years. Still,
Humira’s supremacy was never fated to last forever, and, following the
debut of the first FDA approved Humira biosim—Amgen’s Amjevita—last
January, a successive wave of summer launches gradually eroded Humira
sales in the back half of the year.
For all of 2023, Humira brought home worldwide revenues of $14.4 billion, representing a 32% drop from
the $21.2 billion sum the drug generated in 2022. The pace of erosion
kicked up a notch during the final quarter of 2023, when Humira sales
plunged nearly 41% to $3.3 billion globally.
At the top of 2023, Amgen deployed its biosimilar Amjevita, which came equipped with several months of
biosim exclusivity on the U.S. market thanks to a 2017 settlement with AbbVie. But AbbVie hadn’t thrown in the towel just yet, with
the company’s soon-to-retire CEO Richard Gonzalez noting at the 2023 J.P. Morgan Healthcare Conference that his company was
well prepared to fight the competition and had secured broad 2023
formulary access for Humira with “all of the major” players.
Soon after, in February 2023, Gonzalez told investors that while it was still early days, his company was
“comfortable with how things [were] playing out” in terms of biosimilar
competition. At the time, he said that the most “significant impact” on
Humira going forward would be the price.
By the end of 2023’s second quarter, Humira’s sales had slipped 25%,
though Gonzalez continued to stress that the situation was playing out “as projected, and slightly
better than our planning assumptions."
Following Amgen’s Amjevita rollout, a tranche of additional Humira
biosimilars hit the scene last summer, including Boehringer Ingelheim’s
Cyltezo, Sandoz’s Hyrimoz, Biocon’s Hulio and Coherus BioSciences’
Yusimry.
According to a September survey from Spherix Global Insights, Humira over
the course of 2023 faced “continued erosion” in favor of a “growing embrace of these diverse
biosimilars.”
Still, Spherix cautioned that prescribers had “not wholly warmed to these
newcomers,” pointing out that dermatologists in particular showed the
“highest degree of stated resistance to change,” while rheumatologists
reported the least actual erosion to AbbVie’s brand-name drug.
While AbbVie escaped 2023 with the Humira situation largely as expected,
the branded offering took a hit more recently on April 1, 2024, when CVS
Caremark removed AbbVie’s drug from its national commercial formularies in
favor of biosims.
To help weather the biosim assault, AbbVie is looking to its immunology
up-and-comers Rinvoq and Skyrizi to pick up the slack. Earlier this year,
company executives predicted the meds would generate $16 billion in 2024 and exceed more than
$27 billion by 2027.
3. Ozempic
Ozempic's popularity is a big reason Novo Nordisk has become Europe's most valuable company by market capitalization. (Photo illustration by Mario Tama/Getty Images)
Company: Novo Nordisk
2023 sales: 95.7
billion Danish kroner ($14 billion)
Disease: Type 2 diabetes,
cardiovascular risk reduction in diabetes patients
While Novo Nordisk has continued to do gangbusters with its superstar
GLP-1 diabetes med Ozempic (as well as the drug’s obesity sibling Wegovy),
that success proved to be a double-edged sword in 2023, as the Danish
drugmaker grappled incessantly with supply constraints and an influx of
knockoff semaglutide products for cosmetic weight loss.
For all of 2023, Novo’s Ozempic generated 95.7 billion Danish kroner ($14 billion), growing a staggering 66% at
constant currencies year over year. Since its original U.S. approval in late
2017, Ozempic’s star has risen rapidly, with the drug now something of a
household name that’s even been featured as the butt of the joke in skits at
the Oscars and on "Saturday Night Live."
That popularity can be credited, in part, to the drug’s ability to help
patients lose weight—which has spawned a trend of off-label, cosmetic use
that ultimately helped put the critical diabetes drug into shortage for
months.
Last March, following six months of supply constraints on Ozempic, the drug
once again became available in two common, lower doses, according to the U.S. FDA’s drug shortage
database. At the time, Novo told Fierce the ongoing inventory squeeze was
due to “the combination of incredible demand coupled with overall global
supply constraints.”
Since then, Novo has devoted many of its resources toward building out a
more robust supply network for Ozempic as well as Wegovy, both of which are
underpinned by the molecule semaglutide.
In November, Novo said
it would plug 42 billion Danish kroner ($6 billion) into an expansion of its
existing manufacturing facilities in Kalundborg, Denmark, with the primary
goal to increase capacity for active pharmaceutical ingredients, including
the semaglutide used in Ozempic and Wegovy as well as Ozempic’s oral
counterpart Rybelsus.
At the time, Novo’s CEO Lars Fruergaard Jørgensen noted his company was far
from done with expansions, stressing that the company would “continuously
have to invest.”
Elsewhere, Novo has telegraphed massive manufacturing projects for GLP-1
capacity at plants in France and Ireland, too.
And, while Novo struggles to keep up with Ozempic demand, compounding
pharmacies and counterfeiters have picked up the slack—much to Novo and
regulators’ chagrin.
Last May, the FDA warned that some compounding pharmacies, which are permitted to make drugs
during times of shortage, were using unauthorized versions of Ozempic’s
active ingredient semaglutide. Novo Nordisk subsequently cracked down on the
issue by filing suit against five such pharmacies in June.
Toward the end of the year, meanwhile, the FDA and Novo warned that
counterfeit versions of the med—aka Faux-zempic—had
wormed
their way into the “legitimate” U.S. supply chain.
Related: Best Natural Ozempic Alternatives
4. Eliquis
Eliquis and its direct competitor Xarelto were picked for Medicare price
negotiations under the Inflation Reduction Act.
Companies: Bristol Myers Squibb, Pfizer
2023 sales: $12.9 billion
Diseases: Non-valvular atrial fibrillation, deep vein thrombosis and pulmonary
embolism
As industry watchers had expected, Bristol Myers Squibb and Pfizer’s blood
thinner Eliquis was selected last year as one of the first 10 medicines
subject to Medicare price adjustments beginning in 2026 under the Inflation
Reduction Act (IRA).
In 2023, BMS reported $12 billion in Eliquis net product sales, up 4% year
over year. BMS is the principal for end-product sales in the companies'
partnership in all of the major markets, including the U.S., large countries
in Europe, China and Japan. The New Jersey pharma also booked $5.8 billion in
profit-sharing expenses to Pfizer.
For its part, Pfizer reported $6.7 billion from Eliquis direct sales and
alliance revenues, which also marked an increase of 4%. Pfizer holds full
commercial rights in certain small countries.
Eliquis has been leading in the factor Xa inhibitor market against Bayer and
Johnson & Johnson’s Xarelto, which has also been picked for IRA price
negotiations.
To defend their drugs, BMS and J&J brought legal challenges against the
IRA, but a New Jersey federal judge recently
tossed their lawsuits. The two firms said they would appeal the decisions.
Xarelto ranked No. 12 in Fierce Pharma's top-selling drugs report based on
2021 sales, but it has now fallen out of the rankings. The drug’s 2023 sales
declined in the U.S. because of an unfavorable patient mix and access changes,
and it dropped outside the U.S. thanks to generic erosion.
Eliquis, facing generic competition in the U.K. and Canada, posted a 10%
decline in BMS' share of ex-U.S. markets last year. On the flip side, the U.S.
component of BMS’ Eliquis sales increased by 10%.
Overall, the drug continued to be the top oral anticoagulant globally, and BMS
still expects “strong growth” in the U.S. this year, Chief Financial Officer
David Elkins said on the company’s fourth-quarter earnings call in February.
When asked whether the expected Medicare price reduction would affect
commercial payers, BMS' chief commercialization officer, Adam Lenkowsky, said
the company doesn’t have to yield to that kind of demand.
In the U.S., Eliqius’ composition of matter patent is slated to expire in
2026, and a formulation patent is set to expire in 2031. Both have been
challenged by generic companies. Legal settlements have pushed the generics’
launch date to April 1, 2028, according to BMS’ annual securities filing.
While Eliquis’ days of growth are numbered, BMS has turned to dealmaking to
beef up its cardiovascular offerings. The blockbuster hopeful obstructive
hypertrophic cardiomyopathy drug Camzyos, which BMS got from its $13.1 billion
acquisition of MyoKardia,
bagged its first FDA approval in 2022. And the New Jersey pharma last
year
bought back Asian rights to the drug from the
disbanding LianBio.
BMS also has a
partnership with antibody-oligonucleotide conjugate specialist Avidity Biosciences
involving up to five cardiovascular targets.
5. Biktarvy
Biktarvy's revenues of $11.8 billion accounted for more than half of Gilead
Sciences' entire HIV franchise. (Gilead Sciences)
Company: Gilead Sciences
2023 sales: $11.8 billion
Disease: HIV
When it comes to HIV drug sales, no product comes close to Gilead Sciences'
Biktarvy.
2023 marked another year of sales dominance for the
triple drug cocktail. By the end of the year, the crown jewel of Gilead’s HIV
portfolio claimed 49% of the U.S. market share in HIV, with share gains that
“once again outpaced all other branded regimens for HIV treatment,” Gilead's
chief commercial officer, Johanna Mercier, pointed out during a
company
presentation (PDF) in February.
On its own, the med’s
sales of $11.8 billion accounted for nearly 44% of Gilead’s overall product
sales last year and more than half of the company's HIV franchise. Despite the
high level of sales, Biktarvy was still able to deliver 14% revenue
growth in 2023.
Gilead has long been buoyed by its HIV drug franchise, which is a solid pillar
to lean on as the drugmaker forays further into the oncology space with its
cell therapies and antibody-drug conjugate Trodelvy.
This year, Gilead's HIV sales, and Biktarvy in turn, are expected to grow some
4%, reflecting the usual Biktarvy market share boost and an annual demand
increase.
Within the company’s HIV franchise, Biktarvy is complemented by Gilead’s
preexposure prophylaxis med Descovy. Biktarvy is made up of a three-part
combination of Descovy, which joins emtricitabine and tenofovir alafenamide,
plus integrase inhibitor bictegravir.
Back when Biktarvy first scored FDA approval in 2018, the most optimistic
analysts
projected peak sales to reach $10 billion. Biktarvy crossed that $10 billion
barrier for the first time in 2022.
While competing with Biktarvy is a daunting battle, Gilead's rival GSK has
long eyed capturing more of the market. Still, Gilead was the clear sales
winner in 2023 as Biktarvy alone trumped GSK’s HIV revenue of 6.4 billion
pounds sterling ($8 billion).
But GSK and its Johnson & Johnson partnered long-acting treatment Cabenuva
could sneak up on the once-daily Biktarvy with a convenience edge. Last July,
the partners reported results from a
switching study showing that 90% of patients who responded to a GSK questionnaire said
they preferred Cabenuva over Biktarvy.
Even so, it’s unlikely that any HIV med will topple Biktarvy in 2024. The med
just scored a label
expansion from the FDA allowing its use in pregnant adults with HIV. Not only can
that indication add new patients, it can allow the medicine to retain current
users who become pregnant.
Earlier this year, another
approval added patients with suppressed viral loads and M184V/I resistance,
which is a common form of treatment resistance.
6. Dupixent
Even after beating all sales estimates, Dupixent doesn't appear to be slowing
down anytime soon. (Sanofi)
Company: Regeneron and Sanofi
2023 sales: $11.6 billion
Disease:
Atopic dermatitis, asthma, rhinosinusitis, eosinophilic esophagitis and
prurigo nodularis
Upon its approval in 2017, analysts were
effusive about the game-changing future of Dupixent (dupilumab) and hailed its
sales potential at $3 billion-plus. Geoffrey Porges, then an analyst at
Leerink Partners, bet the over,
estimating the drug's peak sales would reach $5 billion.
Seven years later, the interleukin inhibitor has blown away all predictions.
In 2023, Dupixent raked in $11.6 billion, vaulted into the top 10 and
now
carries a more ambitious estimate. According to Cantor Fitzgerald analyst Josh
Schimmer, Dupixent could top the $20 billion mark by the end of the decade,
which would put it in rarefied air with AbbVie’s Humira and Merck’s cancer
powerhouse Keytruda.
The latest boost comes as Regeneron and Sanofi appear to be closing in on an
FDA approval to treat chronic obstructive pulmonary disease (COPD). It would
be the first significant treatment advance in the elusive indication in more
than a decade and the first biologic approved for COPD. Schimmer believes the
nod would add $2.5 billion in peak sales for Regeneron in the U.S. and another
$1 billion for Sanofi, which commercializes Dupixent in the rest of the world.
For all its success, Dupixent isn’t undefeated. In October 2023, the
FDA
rejected it for chronic spontaneous urticaria (CSU), a severe inflammatory
condition that causes hives, deep swelling on or under the skin and persistent
itch. While the U.S. regulator asked the companies for more efficacy
data—which are expected to come from a separate trial in late 2024—the results
were good enough to pass muster in Japan, where it has been
approved for CSU as an add-on treatment with antihistamines.
When the FDA first signed off on Dupixent, Porges characterized Dupixent as
“life transforming” for many patients with atopic dermatitis (AD). In addition
to adding key indications, including asthma in 2018, Regeneron and Dupixent
have expanded the patient population by showing the treatment is safe for
children.
In AD, they gained nods to treat adolescents (2019), then kids ages 6 to 11
(2020), followed by an OK for children as young as 6 months old (2022). The
companies also have expanded their approvals for asthma and eosinophilic
esophagitis to children as young as ages 6 and 1, respectively.
With these expansions, Dupixent’s sales have skyrocketed each year, from $2.3
billion in 2019 to $4 billion in 2020 to $6.2 billion in 2021 and $9.8
billion in 2022.
7. Comirnaty
Once the world's bestselling biopharma product, Comirnaty sales fell quickly
as the pandemic eased. (Photo by Karwai Tang/Getty Images)
Company: Pfizer and BioNTech
2023 sales: $11.2 billion
Disease:
COVID-19
For nine straight years, AbbVie’s Humira was the top-selling drug in the
world. But then the coronavirus arrived. Six days after the World Health
Organization declared the worldwide pandemic, Pfizer and BioNTech signed a
partnership to develop a COVID vaccine, and, nine months later, the FDA
approved their shot for emergency use.
In 2021, Comirnaty generated sales of $36.8 billion, which was the most ever
in a single year for a pharmaceutical product. Then, in 2022, the shot went
one better, logging sales of $37.8 billion. Over the two years, Pfizer and
BioNTech more than doubled the sales of their lone serious competitor Moderna,
which sold $36 billion of its Spikevax vaccine.
In 2023, as the pandemic transitioned into the endemic stage, the companies
failed to fully anticipate the plummeting demand for their shots. In October,
Pfizer slashed $9 billion from its annual revenue projection, admitting that
sales of its COVID products—including antiviral treatment Paxlovid—came up far
short of its expectations.
For 2024, Pfizer projects Comirnaty sales to reach $5 billion, which is short
of Wall Street’s estimate. It’s also shy of the company’s own prediction that
vaccine sales would be in line with what they were in 2023. CEO Albert Bourla,
Ph.D.,
explained that the company wanted to be “conservative” and offer a “good floor.”
“We want to be reliable so that we will not create again uncertainty, which
was the case early this year when our estimates were way higher than in
reality,” Bourla said in December.
In the first quarter of 2024, Comirnaty generated sales of $354 million, with
Pfizer explaining that it expects 90% of the vaccine’s revenue to come in the
second half of the year and mostly in the fourth quarter because of the
seasonality of demand for COVID vaccinations.
Pfizer’s COVID-19 vaccine partner BioNTech also
reported a massive first-quarter slide for Comirnaty, with sales down 85% to 188
million euros ($202 million). The company, whose only commercial product is
Comirnaty, also recorded a net loss of 315 million euros ($339 million) in the
period, compared to a profit of 502 million euros ($543 million) in the first
quarter of 2023.
For 2024, BioNTech is sticking by its overall revenue forecast of
2.5 billion euros ($2.7 billion) to 3.1 billion euros ($3.3
billion).
8. Stelara
Amgen’s biosimilar is expected to be the first Stelara copycat to rear its
head in the U.S. next year. (Johnson & Johnson)
Company: Johnson & Johnson
2023 sales: $10.9 billion
Disease: Plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative
colitis
While Johnson & Johnson’s antibody star Stelara continued to rake in
megablockbuster sales last year, 2023 marked something of a last hurrah for
the immunology medicine.
That's because J&J spent much of the year inking patent settlements with
biosimilar challengers Amgen, Samsung Bioepis, Sandoz, Teva and Alvotech, in
turn clearing the way for biologic copycats of its lucrative drug to hit the
scene in the U.S. starting in early 2025.
Already, in early 2024, Stelara has been superseded as J&J's top drug by
sales by multiple myeloma offering Darzalex, which is still enjoying
double-digit sales growth.
Over the course of 2023, Stelara
generated nearly $10.9 billion in total worldwide sales, growing its market share
and displaying continued strength in inflammatory bowel disease in particular,
J&J
noted in its full-year earnings report in January. That performance was
largely to be expected, as J&J’s chief financial officer Joe Wolk
suggested in early 2023 that Stelara would continue to chart volume gains in the
U.S. up to the med’s tumble over the patent cliff.
The CFO has said he expects European biosimilars to Stelara to start taking a
bite out of sales in the second half of 2024, while U.S. challengers aren’t
expected to emerge until the start of the following year.
Amgen’s ustekinumab biosimilar—
approved with an interchangeability tag under the brand name Wezlana in
November—will be the first Stelara copycat to rear its head in the U.S. next
year. Under a settlement with J&J, Amgen is expected to launch Wezlana
stateside “no later than January 1st, 2025.”
Biosimilars from Teva, Sandoz, Celltrion and Fresenius Kabi are expected to
hit the scene in the months following Amgen's launch.
Though Stelara’s days as a megablockbuster are numbered, J&J is counting
on a roster of 25 new and upcoming blockbusters to eventually pick up the
slack. Between 2025 and 2030, J&J has said it
expects that phalanx of novel therapies—including the recent cancer launches
Talvey and Tecvayli—to drive annual pharmaceutical sales growth of 5% to
7%.
9. Opdivo
Opdivo is the perfect example of how a first-to-market product can quickly
lose its edge. (Bristol Myers Squibb)
Companies: Bristol Myers Squibb and Ono Pharmaceutical
2023 sales: $10
billion
Diseases: Melanoma, non-small cell lung cancer, malignant pleural
mesothelioma, kidney cancer, classical Hodgkin lymphoma, head and neck cancer,
bladder cancer, microsatellite instability-high or mismatch repair deficient
colorectal cancer, liver cancer, esophageal cancer, gastric cancer,
gastroesophageal junction cancer
Opdivo generated $10 billion in global sales last year, with $9 billion going
to Bristol Myers Squibb and 148 billion Japanese yen ($1 billion) going to Ono
Pharmaceutical.
As BMS’ second-largest brand, the PD-1 inhibitor continued to grow in 2023,
but it also continued to fall further behind its rival, Merck & Co.’s
Keytruda, which in 2023 became the world’s top-selling medicine.
In the U.S., Opdivo’s revenues grew 10% to $5.3 billion last year. They were
no match for Keytruda’s $15.1 billion in sales in the country, which marked a
19% growth rate year over year.
Opdivo is the perfect example of how a first-to-market product can quickly
lose its edge. In a 2017 Fierce Pharma report citing estimates by Evaluate
Pharma and Chempetitive, Opdivo was
projected to reach $12.6 billion in 2022 sales, almost double Keytruda’s
projection of $6.6 billion for that year.
Things took a sharp turn in 2018, when Keytruda’s
KEYNOTE-189 data in first-line non-small cell lung cancer (NSCLC) forever changed the
competitive landscape between the two PD-1 inhibitors.
When it comes to label expansions, Opdivo has been relatively quiet in the
past two years compared with Keytruda. Earlier this year in March,
Opdivo
got an FDA go-ahead for use alongside chemo for the first-line treatment of bladder cancer.
But the nod was outshined by Keytruda’s combination with Padcev in the same
setting.
In March 2022, Opdivo
became the first immunotherapy allowed for the presurgical treatment of early-stage
non-small cell lung cancer. Then phase 3 data from the CheckMate-77T trial
unveiled in October 2023 further
showed Opdivo’s potential as a continuous therapy used before and after
surgery in NSCLC. As BMS awaits an FDA decision by Oct. 8, Keytruda has
already
secured that neoadjuvant-adjuvant indication.
Opdivo helped BMS achieve another breakthrough in 2022 when it was
approved with the company’s LAG-3 antibody relatlimab in a fixed-dose combo
under the brand name Opdualag. However, the regimen has yet to post any other
major clinical wins beyond its initial melanoma indication.
Also in 2022, BMS and its then-partner Nektar Therapeutics’ plan to boost
Opdivo with the interleukin-2 drug Bempeg
imploded after multiple trial failures. Data released later from a melanoma
trial showed that the Opdivo-Bempeg combo performed even worse than Opdivo
alone. Opdivo is slated to lose U.S. market exclusivity in 2028. BMS is ahead
of Merck with the development of a subcutaneous version of their rival PD-1
drugs. After subcutaneous Opdivo
matched up to its infused version on two co-primary endpoints of the CheckMate-67T
trial in kidney cancer, the FDA recently
accepted BMS’ application for the injection across all of Opdivo’s previously
approved adult indications. The agency plans to decide on the prospect by Feb.
28, 2025.
Injectable Opdivo could become the first subcutaneously administered PD-1/L1
inhibitor in the U.S., and BMS has said it plans to convert about 30% to 40%
of the overall Opdivo market in the U.S. to the under-the-skin formulation.
As BMS deals with several major patent cliffs, the company has beefed up its
oncology capabilities through acquisitions. The immuno-oncology giant
recently bought Mirati Therapeutics for $5.8 billion and got the KRAS inhibitor
Krazati. However, the targeted therapy is being trialed in combination with
Keytruda—not Opdivo—in first-line NSCLC.
Similarly, Ono just
unveiled
a $2.4 billion deal to purchase oncology specialist Deciphera Pharmaceuticals.
Besides the FDA’s approved cancer drug Qinlock, the Japanese pharma will also
gain a kinase inhibitor discovery platform.
10. Darzalex/Darzalex Faspro
Darzalex is part of an armamentarium of multiple myeloma treatments that
J&J has built. (Johnson & Johnson)
Company: Johnson &
Johnson
2023 sales: $9.7 billion
Diseases: Multiple myeloma and
light chain amyloidosis
The Darzalex franchise, including the subcutaneous formulation Darzalex Faspro,
was Johnson & Johnson’s second-largest brand last year. With $9.74
billion in global sales, the multiple myeloma drug accounted for 11.4% of the
pharma and medtech giant’s total revenue haul for the year.
Darzalex secured its initial FDA approval in 2015 as a fourth-line multiple
myeloma treatment and the first monoclonal antibody for the blood cancer. It
entered the first-line setting in 2018 as part of a now outdated combination
including Takeda’s Velcade, the alkylating agent melphalan and the
corticosteroid prednisone.
Much more recently, the J&J drug has shown promise as part of an advanced
combo with Velcade, Bristol Myers Squibb’s Revlimid and the steroid
dexamethasone (VRd). Late last year, the Darzalex-containing four-drug
regimen
showed it could slash the risk of progression or death by 58% versus VRd alone
in first-line myeloma patients who’re eligible for stem cell transplants. The
company filed that combo with the FDA in January and secured a priority
review.
J&J licensed the anti-CD38 antibody from Genmab in 2012 for $55
million upfront and about $80 million in direct investment, plus up to $1
billion in milestones and tiered royalties. Those royalties accounted for 68%
of Genmab’s 16.5 billion Danish kroner ($2.4 billion) in revenue in
2023.
The Darzalex partnership between J&J and Genmab hasn't always been
cordial. In 2020, Genmab
launched an arbitration case against J&J related to Darzalex royalties.
After that attempt was shot down in 2022, Genmab filed a second arbitration
case specifically centered on subcutaneous Darzalex in Europe. The claim was
once again denied, first in April 2023 and then at an appellate arbitrator in
January 2024. Besides its royalty payments to Genmab, J&J also pays
royalties to Halozyme for using the latter company's subcutaneous drug
delivery technology, Enhanze.
In the anti-CD38 space, Darzalex competes with Sanofi’s Sarclisa, which
entered the U.S. market in 2020 as a third-line treatment. In 2021, the
latecomer was greenlighted for use alongside Amgen’s Kyprolis and
dexamethasone for myeloma patients who have tried one to three prior lines
of therapy.
Sarclisa has not been a serious commercial threat to Darzalex. In 2023,
Sarclisa sales grew 37% at constant exchange rates to 381 million
euros ($412 million). Darzalex’s $9.74 billion haul last year marked a 23%
increase at constant currencies.
The two patent families around Darzalex will expire in the U.S. in 2029,
according to J&J’s annual securities filing.
In recent years, the company has build an armamentarium of multiple
myeloma treatments. Besides Darzalex, J&J has BCMA CAR-T therapy
Carvykti—which it licensed from Legend Biotech—and two T-cell engagers,
BCMA-targeted Tecvayli and GPRC5D-directed Talvey, both of which
originated from Genmab.
With those four drugs, J&J believes three out of every four new
myeloma patients could be on one of its offerings by the end of the
decade, CEO Joaquin Duato said during a conference call in July 2023.
Besides the multiple myeloma use, Darzalex Faspro in 2021 received an accelerated approval as part of a combination to treat newly
diagnosed patients with light chain amyloidosis, a rare disease caused by
abnormal build up of the amyloid protein.
Source and Reference: https://www.fiercepharma.com/special-reports/top-20-drugs-worldwide-sales-2023
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